Linking the physical and chemical characteristics of Qdots to their toxicity

描述（由申请人提供）：工程纳米材料正在或拟用于大量商业产品。由于其高度多样的物理和化学特性，以及其体积小，人们对它们可能对人类健康或环境造成危害表示关切。一类重要的ENM是量子点（Qdot），其是由重金属核（例如，CdSe、CdTe、HgTe）组成的发光半导体纳米晶体，其具有根据各种应用所需的特性而变化很大的帽和涂层结构。已知某些特征是纳米颗粒与细胞和组织相互作用的决定因素，包括形状、大小、疏水性和表面电荷。由于这些和其他工程纳米材料的高度可变性，仍然很难预测它们的毒性。基因组学、表观遗传学和生物信息学方面的现代进展，以及具有充分表征的多态性和调控序列的多个近交系小鼠的可用性，使得绘制和预测包括纳米材料在内的许多有毒物质的毒性途径成为可能。本文提出的研究将利用气道暴露于雾化量子点纳米颗粒的体外和体内模型，以1）定义控制其吸收、分布、代谢、排泄和毒性的物理和化学特征; 2）使用多个近交系小鼠，绘制与这些特征相关的毒性途径;和3）将从这些体外和体内模型中获得的信息纳入风险评估范例，用于预测纳米材料对人类的毒性。这些信息不仅将确定哪些物理和化学特性对量子点的不良生物效应很重要，而且还将同时推进纳米材料毒理学和功能表观基因组学领域。这些进展可用于纳米材料的安全设计和制造，以最大限度地提高其在许多应用中的效用。

DESCRIPTION (provided by applicant): Engineered nanomaterials are being used or are being proposed for use in a large number of commercial products. Because of their highly diverse physical and chemical characteristics, and their small size, concerns have been raised regarding their potential to cause harm to human health or the environment. One important class of ENMs are quantum dots (Qdots) which are luminescent semiconductor nanocrystals composed of heavy metal cores (e.g. CdSe, CdTe, HgTe) with cap and coating structures that vary greatly, depending upon the characteristics required for various applications. Certain characteristics are known to be determinants for the interaction of nanoparticles with cells and tissues, including shape, size, hydrophobicity, and surface charge. Because of the highly variable nature of these and other engineered nanomaterials, it will be nonetheless difficult to predict their toxicity. Modern advances in genomics, epigenetics and bioinformatics, and the availability of multiple strains of inbred mice with well characterized polymorphisms and regulatory sequences have made it possible to map and predict toxicity pathways for many toxic substances including nanomaterials. The research proposed herein will utilize in vitro and in vivo models of airway exposure to aerosolized quantum dot nanoparticles to 1) define the physical and chemical characteristics that govern their absorption, distribution, metabolism, excretion and toxicity; 2) using multiple inbred strains of mice, map toxicity pathways associated with these characteristics; and 3) incorporate the information that is obtained from these in vitro and in vivo models into a risk assessment paradigm that will be used to predict nanomaterial toxicity to humans. Such information will not only define which physical and chemical characteristics are important for the adverse biological effects of quantum dots, but will also simultaneously advance the fields of nanomaterial toxicology and functional epigenomics. These advances can then be used in safe design and manufacturing of nanomaterials so as to maximize their utility for many applications.